1. Field of the Invention
This invention is directed to monoclonal antibodies against ganglioside antigens associated with melanoma, hybrid cell lines producing these antibodies, and methods of using these monoclonal antibodies.
2. Description of the Background Art
Gangliosides are a major class of carbohydrate-rich glycolipids of extremely large size and complexity. Gangliosides are usually found on the outer surface of cell membranes, especially among the cells of the nervous system. It has been suggested that gangliosides may function as membrane receptors for growth factors, hormones, and adhesion molecules. In recent years, the possible role of gangliosides as tumor markers has received considerable attention. As a result, investigators have produced monoclonal antibodies which specifically react with gangliosides on the surface of human melanoma (Cheresh, et al., Proceedings of the National Academy of Sciences, U.S.A., 82:5155, 1985; Cheresh, et al., Proceedings of the National Academy of Sciences, U.S.A., 81:5767, 1984; Pukel, et al., Journal of Experimental Medicine, 155:1133, 1982; Cheresh, et al., Journal of Biological Chemistry, 259:7453, 1984), neuroblastoma (Schulz, et al., Cancer Research, 44:5914, 1984), and colon carcinoma (Koprowski, et al., Somatic Cell Genetics, 5:957-972, 1979). Several recent studies have pointed to ganglioside antigen GD3 as being a potential target for immunotherapy in human melanoma (Hellstrom, et al., Proceedings of the National Academy of Sciences, U.S.A., 82:1499, 1985). Previous studies had identified ganlisodie antigen GD2 as another melanoma-associated antigen.
Although ganglioside antigens are present in central nervous tissue, GD2 is greatly enriched in melanoma, brain tumors, neuroblastoma, small cell carcinoma of the lung and other tumors of neuroectodermal origin. Studies on the development of these ganglioside antigens indicate that GD3 is a precursor of GD2 and that the distribution of GD2 and GD3 in various melanomas varies depending upon the severity of the disease. In general, ganglioside antigen GD2 occurs primariliy in advanced primary and metastatic melanoma and is rarely present in normal tissue.
At present the method of choice for the treatment of melanoma and other tumors bearing ganglioside antigens GD2 and GD3 involves excision of the involved malignant tissue. Unfortunately, in advanced stages the accompanying deep tissue invasion by the tumor makes this approach much more difficult due to the increase in surgical trauma and the amount of tissue that may be excised. Since the survival rate of malignant melanoma is inversely related to the level of invasion of the host tissue present clinical strategy has no choice but to resort to surgery. However, in advanced stages the increased dissemination of the tumor creates a situation in which surgical excision is much less likely to be successful. Consequently, this results in a greatly reduced prognosis for those patients having advanced malignancies.